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In a randomized trial, over 2700 patients with obstructive sleep apnea and cardiovascular disease were assigned to CPAP plus usual care or to usual care alone. At a mean of 3.7 years, the rate of adverse cardiovascular events did not differ significantly between the groups. Obstructive sleep apnea causes episodic hypoxemia and nocturnal sympathetic nervous system activation 1 and elevates blood pressure 2 and markers of oxidative stress, inflammation, and hypercoagulation. 3 , 4 Large negative intrathoracic pressure swings also impose mechanical stress on the heart and great vessels. 5 – 7 Population-based and sleep-clinic–based cohort studies have shown an association between obstructive sleep apnea and cardiovascular events, 8 – 16 particularly stroke. 17 Randomized, controlled trials have shown that treatment with continuous positive airway pressure (CPAP) lowers systolic blood pressure by 2 to 3 mm Hg in patients with normotensive obstructive sleep apnea 18 and by 6 to 7 mm Hg in patients with . . .

Mammalian target of rapamycin （mTOR） is a core component of raptor-mTOR （mTORCI） and rictor-mTOR （mTORC2） complexes that control diverse cellular processes. Both mTORC1 and mTORC2 regulate several elements downstream of type I insulin-like growth factor receptor （IGF-IR） and insulin receptor （InsR）. However, it is unknown whether and how roTOR regulates IGF-IR and InsR themselves. Here we show that mTOR possesses unex- pected tyrosine kinase activity and activates IGF-IR/InsR. Rapamycin induces the tyrosine phosphorylation and ac- tivation of IGF-IR/InsR, which is largely dependent on rictor and mTOIL Moreover, mTORC2 promotes ligand-induced activation of IGF-IR/InsR. IGF- and insulin-induced IGF-IR/InsR phosphorylation is significantly compromised in rictor-null cells. Insulin receptor substrate （IRS） directly interacts with SIN1 thereby recruiting mTORC2 to IGF-IR/InsR and promoting rapamyeinor ligand-induced phosphorylation of IGF-IR/InsR. mTOR exhibits tyrosine kinase activity towards the general tyrosine kinase substrate poly（Glu-Tyr） and IGF-IR/InsR. Both recombi- nant mTOR and immunoprecipitated mTORC2 phosphorylate IGF-IR and InsR on Tyr1131/1136 and Tyr1146/llS1, respectively. These effects are independent of the intrinsic kinase activity of IGF-IR/InsR, as determined by assays on kinase-dead IGF-IR/InsR mutants. While both rictor and mTOR immunoprecitates from rictor＋/＋ MCF-10A cells exhibit tyrosine kinase activity towards IGF-IR and InsR, mTOR immunoprecipitates from rictor-/- MCF-10A cells do not induce IGF-IR and InsR phosphorylation. Phosphorylation-deficient mutation of residue Tyrll31 in IGF-IR or Tyrl146 in InsR abrogates the activation of IGF-IR/InsR by mTOR. Finally, overexpression of rictor promotes IGF-induced cell proliferation. Our work identifies mTOR as a dual-specificity kinase and clarifies how mTORC2 promotes IGF-IR/InsR activation.

Although septal myectomy is the preferred treatment for medication-refractory hypertrophic obstructive cardiomyopathy (HOCM), the procedure remains subjective. A preoperative planning procedure is proposed using computational fluid dynamics simulations and shape optimization to assist in the objective assessment of the adequacy of the resection. 3 patients with HOCM were chosen for the application of the proposed procedure. The geometries of the preoperative left ventricular outflow tract (LVOT) of patients in the systolic phase were reconstructed from medical images. Computaional fluid dynamics (CFD) simulations were performed to assess hemodynamics within LVOT. Sensitivity analysis was performed to determine the resection extent on the septal wall, and the depth of the resection was optimized to relieve LVOT obstruction while minimizing damage to the septum. The optimized resection was then transferred from systole to diastole to provide surgeons with instructive guidance for septal myectomy. Comparison between preoperative and postoperative hemodynamics showed an evident improvement with respect to the pressure gradient throughout the LVOT. The resected myocardium in the diastolic phase is more extended and thinner than its state in the systolic phase. The proposed preoperative planning procedure may be a viable addition to the current preoperative assessment of patients with HOCM.

Six new polyene carboxylic acids named serpentemycins E–J (1–6), together with three known analogs (7–9), were isolated from the fermentation medium of Streptomyces sp. TB060207, which was isolated from arid soil collected from Tibet, China. The structures of the new compounds were elucidated mainly on the basis of HR-ESI-MS and NMR spectroscopic analyses. The inhibitory activities of compounds 1–9 against NO production in LPS-activated RAW264.7 cells were evaluated. Compound 9 has an inhibition rate of 87.09% to 60.53% at concentrations ranging from 5.0 to 40.0 µM.

Hemodynamic analysis based on computational fluid dynamics (CFD) modelling is expected to improve risk stratification for patients with aortic aneurysms and dissections. However, the parameter settings in CFD simulations involve considerable variability and uncertainty. Additionally, the exact relationship between hemodynamic features and disease progression remains unclear. These challenges limit the clinical application of aortic hemodynamic models. This review presents a detailed overview of the workflow for CFD-based aortic hemodynamic analysis, with a focus on recent advancements in the field. We also conducted a systematic review of 27 studies with large sample sizes (n > 5) that examine the hemodynamic characteristics of aortic aneurysms and dissections. Some studies identified consistent relationships between hemodynamic features and disease progression, reinforcing the potential for clinical application of aortic hemodynamic models. However, limitations such as small sample sizes and oversimplified patient-specific models remain. These findings emphasize the need for larger, more detailed studies to refine CFD modelling strategies, strengthen the connection between hemodynamics and diseases, and ultimately facilitate the clinical use of aortic hemodynamic models in disease management.

Acyl homoserine lactone (AHL)-based quorum sensing commonly refers to cell density-dependent regulatory mechanisms found in bacteria. However, beyond bacteria, this cell-to-cell communication mechanism is poorly understood. Here we show that a methanogenic archaeon, Methanosaeta harundinacea 6Ac, encodes an active quorum sensing system that is used to regulate cell assembly and carbon metabolic flux. The methanogen 6Ac showed a cell density-dependent physiology transition, which was related to the AHL present in the spent culture and the filI gene-encoded AHL synthase. Through extensive chemical analyses, a new class of carboxylated AHLs synthesized by FilI protein was identified. These carboxylated AHLs facilitated the transition from a short cell to filamentous growth, with an altered carbon metabolic flux that favoured the conversion of acetate to methane and a reduced yield in cellular biomass. The transcriptomes of the filaments and the short cell forms differed with gene expression profiles consistent with the physiology. In the filaments, genes encoding the initial enzymes in the methanogenesis pathway were upregulated, whereas those for cellular carbon assimilation were downregulated. A luxI–luxR ortholog filI–filR was present in the genome of strain 6Ac. The carboxylated AHLs were also detected in other methanogen cultures and putative filI orthologs were identified in other methanogenic genomes as well. This discovery of AHL-based quorum sensing systems in methanogenic archaea implies that quorum sensing mechanisms are universal among prokaryotes.

Background Osteoporotic fractures (OPF) have a serious impact on the health of patients. It is of great importance to investigate the diagnostic effect of SNH16 on OPF and the mechanism of action to promote fracture healing. Methods 132 OPF patients and 128 OP patients were included. The levels of SNHG16, Col I, RUNX2 and OCN were evaluated by RT-qPCR. The diagnostic value of SNHG16 was evaluated by ROC curve. Cell proliferation ability was assessed by CCK-8, and apoptosis rate was detected by flow cytometry. ENCORI was used to predict the binding sites of SNHG16 with downstream target genes. DLR assay demonstrated the targeting relationship between SNHG16 and miR-432-5p. Results SNHG16 was poorly expressed in OPF patients compared with OP patients, and its expression was lower in patients with delayed healing. In addition, in the OPF, OPG level was decreased, the level of RANKL was increased, and the balance of bone resorption formation is disrupted leading to fractures. Knockdown of SNHG16 results in decreased cell proliferation and increased apoptosis, and high SNHG16 expression decreases miR-432-5p expression, thereby increasing the levels of Col I, RUNX2 and OCN. Conclusion Increasing SNHG16 can reduce the level of miR-432-5p thereby increasing the level of osteosynthesis proteins and restoring cellular activity, thereby promoting fracture healing.

Although intensively studied in patients with cardiovascular diseases (CVDs), the prognostic value of diastolic blood pressure (DBP) has little been elucidated in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study aimed to reveal the prognostic value of DBP in AECOPD patients. Inpatients with AECOPD were prospectively enrolled from 10 medical centers in China between September 2017 and July 2021. DBP was measured on admission. The primary outcome was all-cause in-hospital mortality; invasive mechanical ventilation and intensive care unit (ICU) admission were secondary outcomes. Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regressions were used to identify independent prognostic factors and calculate the hazard ratio (HR) and 95% confidence interval (CI) for adverse outcomes. Among 13,633 included patients with AECOPD, 197 (1.45%) died during their hospital stay. Multivariable Cox regression analysis showed that low DBP on admission (<70 mmHg) was associated with increased risk of in-hospital mortality (HR = 2.16, 95% CI: 1.53-3.05, Z = 4.37, P <0.01), invasive mechanical ventilation (HR = 1.65, 95% CI: 1.32-2.05, Z = 19.67, P <0.01), and ICU admission (HR = 1.45, 95% CI: 1.24-1.69, Z = 22.08, P <0.01) in the overall cohort. Similar findings were observed in subgroups with or without CVDs, except for invasive mechanical ventilation in the subgroup with CVDs. When DBP was further categorized in 5-mmHg increments from <50 mmHg to ≥100 mmHg, and 75 to <80 mmHg was taken as reference, HRs for in-hospital mortality increased almost linearly with decreased DBP in the overall cohort and subgroups of patients with CVDs; higher DBP was not associated with the risk of in-hospital mortality. Low on-admission DBP, particularly <70 mmHg, was associated with an increased risk of adverse outcomes among inpatients with AECOPD, with or without CVDs, which may serve as a convenient predictor of poor prognosis in these patients. Chinese Clinical Trail Registry, No. ChiCTR2100044625.

Background The morbidity and mortality among hospital inpatients with AECOPD and CVDs remains unacceptably high. Currently, no risk score for predicting mortality has been specifically developed in patients with AECOPD and CVDs. We therefore aimed to derive and validate a simple clinical risk score to assess individuals’ risk of poor prognosis. Study design and methods We evaluated inpatients with AECOPD and CVDs in a prospective, noninterventional, multicenter cohort study. We used multivariable logistic regression analysis to identify the independent prognostic risk factors and created a risk score model according to patients’ data from a derivation cohort. Discrimination was evaluated by the area under the receiver-operating characteristic curve (AUC), and calibration was assessed by the Hosmer–Lemeshow goodness-of-fit test. The model was validated and compared with the BAP-65, CURB-65, DECAF and NIVO models in a validation cohort. Results We derived a combined risk score, the ABCDMP score, that included the following variables: age > 75 years, BUN > 7 mmol/L, consolidation, diastolic blood pressure ≤ 60 mmHg, mental status altered, and pulse > 109 beats/min. Discrimination (AUC 0.847, 95% CI, 0.805–0.890) and calibration (Hosmer‒Lemeshow statistic, P  = 0.142) were good in the derivation cohort and similar in the validation cohort (AUC 0.811, 95% CI, 0.755–0.868). The ABCDMP score had significantly better predictivity for in-hospital mortality than the BAP-65, CURB-65, DECAF, and NIVO scores (all P  < 0.001). Additionally, the new score also had moderate predictive performance for 3-year mortality and can be used to stratify patients into different management groups. Conclusions The ABCDMP risk score could help predict mortality in AECOPD and CVDs patients and guide further clinical research on risk-based treatment. Clinical trial registration Chinese Clinical Trail Registry NO.:ChiCTR2100044625; URL: http://www.chictr.org.cn/showproj.aspx?proj=121626 .

To advance the development of green building materials and achieve high-value utilization of waste resources, this study investigates the mechanistic influence of incorporating waste wood fibers on the mechanical and thermal insulation properties of lightweight mortar. Five fiber contents were designed—0%, 0.4%, 0.8%, 1.2%, and 1.6%—to systematically evaluate their effects on compressive strength, flexural strength, and tensile bond strength, as well as thermal conductivity, pore structure, and microstructural interfaces. The results demonstrate that at low fiber dosages (particularly 0.4% and 0.8%), wood fibers can significantly enhance both the mechanical strength and thermal insulation performance of mortar. Specifically, at a fiber content of 0.8%, the 28-day compressive strength increased by 10.62%, and the flexural strength by 23.8%; the tensile bond strength reached its peak at 0.4%, with a 14.8% improvement. The lowest thermal conductivity recorded was 0.16 W/(m·K), accompanied by a remarkable 61.9% reduction in porosity compared to the control group. Low-field nuclear magnetic resonance (LF-NMR) analysis revealed that wood fiber incorporation markedly increased the proportion of capillary pores, reduced total porosity, and enhanced mortar compactness; scanning electron microscopy (SEM) observations further indicated that the honeycomb-like morphology and surface roughness of wood fibers substantially improved interfacial bonding performance and microcrack-bridging capacity. The findings suggest that an optimal fiber content—recommended to not exceed 0.8%—can synergistically improve the mechanical and thermal insulation properties of lightweight mortar, providing both theoretical support and practical guidance for its application in green building wall materials.